Gena Glickman

Light therapy for seasonal affective disorder with blue narrow-band light-emitting diodes (LEDs).

BACKGROUND While light has proven an effective treatment for Seasonal Affective Disorder (SAD), an optimal wavelength combination has not been determined. Short wavelength light (blue) has demonstrated potency as a stimulus for acute melatonin suppression and circadian phase shifting. METHODS This study tested the efficacy of short wavelength light therapy for SAD. Blue light emitting diode (LED) units produced 468 nm light at 607 microW/cm2 (27 nm half-peak bandwidth); dim red LED units provided 654 nm at 34 microW/cm2 (21 nm half-peak bandwidth). Patients with major depression with a seasonal pattern, a score of > or =20 on the Structured Interview Guide for the Hamilton Depression Rating Scale-SAD version (SIGH-SAD) and normal sleeping patterns (routine bedtimes between 10:00 pm and midnight) received 45 minutes of morning light treatment daily for 3 weeks. Twenty-four patients completed treatment following random assignment of condition (blue vs. red light). The SIGH-SAD was administered weekly. RESULTS Mixed-effects analyses of covariance determined that the short wavelength light treatment decreased SIGH-SAD scores significantly more than the dimmer red light condition (F = 6.45, p = .019 for average over the post-treatment times). CONCLUSIONS Narrow bandwidth blue light at 607 microW/cm2 outperforms dimmer red light in reversing symptoms of major depression with a seasonal pattern.

Sensitivity of the Human Circadian System to Short-Wavelength (420-nm) Light

The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female (n = 14) and male (n = 12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects (n = 8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 1010 to 1014 photons/cm 2/sec and 1 dark exposure control night. In the other study, subjects (n = 18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 × 1013 photons/cm2/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression (p < 0.001) with a half-saturation constant of 2.74 × 1011 photons/cm2/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin (p < 0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications.

Circadian rhythms and sleep in children with autism

A growing body of research has identified significant sleep problems in children with autism. Disturbed sleep-wake patterns and abnormal hormone profiles in children with autism suggest an underlying impairment of the circadian timing system. Reviewing normal and dysfunctional relationships between sleep and circadian rhythms will enable comparisons to sleep problems in children with autism, prompt a reexamination of existing literature and offer suggestions for future inquiry. In addition, sleep and circadian rhythms continue to change over the course of development even in typical, healthy humans. Therefore, exploring the dynamic relationship between circadian rhythms and sleep throughout development provides valuable insight into those sleep problems associated with autism. Ultimately, a better understanding of sleep and circadian rhythms in children with autism may help guide appropriate treatment strategies and minimize the negative impact of these disturbances on both the children and their families.

Inferior Retinal Light Exposure Is More Effective than Superior Retinal Exposure in Suppressing Melatonin in Humans

Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p [#003C] 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

Photic Sensitivity for Circadian Response to Light Varies with Photoperiod

The response of the circadian system to light varies markedly depending on photic history. Under short day lengths, hamsters exhibit larger maximal light-induced phase shifts as compared with those under longer photoperiods. However, effects of photoperiod length on sensitivity to subsaturating light remain unknown. Here, Syrian hamsters were entrained to long or short photoperiods and subsequently exposed to a 15-min light pulse across a range of irradiances (0-68.03 µW/cm2) to phase shift activity rhythms. Phase advances exhibited a dose response, with increasing irradiances eliciting greater phase resetting in both conditions. Photic sensitivity, as measured by the half-saturation constant, was increased 40-fold in the short photoperiod condition. In addition, irradiances that generated similar phase advances under short and long days produced equivalent phase delays, and equal photon doses produced larger delays in the short photoperiod condition. Mechanistically, equivalent light exposure induced greater pERK, PER1, and cFOS immunoreactivity in the suprachiasmatic nuclei of animals under shorter days. Patterns of immunoreactivity in all 3 proteins were related to the size of the phase shift rather than the intensity of the photic stimulus, suggesting that photoperiod modulation of light sensitivity lies upstream of these events within the signal transduction cascade. This modulation of light sensitivity by photoperiod means that considerably less light is necessary to elicit a circadian response under the relatively shorter days of winter, extending upon the known seasonal changes in sensitivity of sensory systems. Further characterizing the mechanisms by which photoperiod alters photic response may provide a potent tool for optimizing light treatment for circadian and affective disorders in humans.

Twice Daily Melatonin Peaks in Siberian but not Syrian Hamsters under 24 h Light:Dark:Light:Dark Cycles

The daily pattern of blood-borne melatonin varies seasonally under the control of a multi-oscillator circadian pacemaker. Here we examine patterns of melatonin secretion and locomotor activity in Siberian and Syrian hamsters entrained to bimodal LDLD8:4:8:4 and LD20:4 lighting schedules that facilitate novel temporal arrangements of component circadian oscillators. Under LDLD, both species robustly bifurcated wheel-running activity in distinct day scotophase (DS) and night scotophase (NS) bouts. Siberian hamsters displayed significant melatonin increases during each scotophase in LDLD, and in the single daily scotophase of LD20:4. The bimodal melatonin secretion pattern persisted in acutely extended 16 h scotophases. Syrian hamsters, in contrast, showed no significant increases in plasma melatonin during either scotophase of LDLD8:4:8:4 or in LD20:4. In this species, detectable levels were observed only when the DS of LDLD was acutely extended to yield 16 h of darkness. Established species differences in the phase lag of nocturnal melatonin secretion relative to activity onset may underlie the above contrast: In non-bifurcated entrainment to 24 h LD cycles, Siberian hamsters show increased melatonin secretion within ∼2 h after activity onset, whereas in Syrian hamsters, detectable melatonin secretion phase lags activity onset and the L/D transition by at least 4 h. The present results provide new evidence indicating multi-oscillator regulation of the waveform of melatonin secretion, specifically, the circadian control of the onset, offset and duration of nocturnal secretion.

Increased photic sensitivity for phase resetting but not melatonin suppression in Siberian hamsters under short photoperiods.

Light regulates a variety of behavioral and physiological processes, including activity rhythms and hormone secretory patterns. Seasonal changes in the proportion of light in a day (photoperiod) further modulate those functions. Recently, short (SP) versus long days (LP) were found to markedly increase light sensitivity for phase shifting in Syrian hamsters. To our knowledge, photoperiod effects on light sensitivity have not been studied in other rodents, nor is it known if they generalize to other circadian responses. We tested whether photic phase shifting and melatonin suppression vary in Siberian hamsters maintained under LP or SP. Select irradiances of light were administered, and shifts in activity were determined. Photic sensitivity for melatonin suppression was examined in a separate group of animals via pulses of light across a 4 log-unit photon density range, with post-pulse plasma melatonin levels determined via RIA. Phase shifting and melatonin suppression were greater at higher irradiances for both LP and SP. The lower irradiance condition was below threshold for phase shifts in LP but not SP. Melatonin suppression did not vary by photoperiod, and the half saturation constant for fitted sigmoid curves was similar under LP and SP. Thus, the photoperiodic modulation of light sensitivity for phase shifting is conserved across two hamster genera. The dissociation of photoperiod effects on photic phase shifting and melatonin suppression suggests that the modulation of sensitivity occurs downstream of the common retinal input pathway. Understanding the mechanistic basis for this plasticity may yield therapeutic targets for optimizing light therapy practices.